Dual Inhibition of EGFR With Afatinib and Cetuximab in the Treatment of Advanced Squamous Cell Cancers of the Head and Neck

Inclusion Criteria: * Histologically confirmed squamous cell carcinoma of the head and neck that is metastatic, recurrent or locally advanced and not treatable with curative intent. * Previous treatment with a platinum-based regimen or immune checkpoint inhibitor or both.2-week washout period prior to treatment start will be required. * Patients who have experienced progression of disease within 6 months following completion of a platinum-based chemoradiation in the definitive or adjuvant setting will be permitted. * Prior cetuximab permitted if it was given as part of multi-modality therapy for initial treatment of locally advanced disease. * Measurable disease based on RECIST v 1.1. Baseline measurements and evaluations must be obtained within 4 weeks of enrollment. Disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual carcinoma following radiation therapy. * ECOG performance status ≤2 * Adequate organ function, defined as all of the following: * Hemoglobin ≥ 8 g/dl. * Absolute neutrophil count (ANC) ≥1000 / mm3. * Platelet count ≥75,000 / mm3. * Estimated creatinine clearance \> 45ml / min. * Total Bilirubin ≤ 1.5 times upper limit of (institutional/central) normal (Patients with Gilbert's syndrome total bilirubin must be ≤4 times institutional upper limit of normal). * Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤ three times the upper limit of (institutional/central) normal (ULN) (if related to liver metastases ≤ five times ULN). * Ability to understand and the willingness to sign a written informed consent that is consistent with ICH-GCP guidelines. * Negative urine or serum pregnancy test for women of childbearing potential * A second eligibility review will always be provided by a Head and Neck Research Team associated for the New Haven Campus and a third review will be provided by the PI. Exclusion Criteria: * Prior erlotinib, gefitinib or lapatinib therapy or prior exposure to any investigational EGFR or panErbB reversible or irreversible inhibitor or any prior panitumumab or investigational EGFR-directed monoclonal antibody. Cetuximab is permitted if used for locally advanced disease, as long as no disease progression within 6 months. Cetuximab use is not permitted for recurrent/metastatic disease * Radiotherapy within 2 weeks prior to enrollment. Palliative radiation to target organs may be allowed up to 2 weeks prior to enrollment, as long as there are other target lesions that can be monitored for response to study treatment. * Known hypersensitivity to afatinib or its excipients * Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use highly effective methods of birth control prior to study entry, for the duration of study participation and for at least 4 weeks after treatment has ended. * Women who are pregnant, nursing, or who plan to become pregnant while in the trial. * Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug. * Concomitant malignancies at other sites that are being actively treated with systemic therapy * Requiring treatment with any of the prohibited concomitant medications that cannot be stopped for the duration of trial participation. * Clinically significant interstitial lung disease. * Known history of untreated viral hepatitis or HIV. * Patients with parenchymal brain metastases are not eligible, unless they have completed local therapy * Leptomeningeal carcinomatosis